1. Field of the Invention
The present invention relates to a biologically active substance consisting of specific compounds. Further, the present invention relates to a melanin production inhibitor, cell growth activator, anti-bacterial agent, etc. containing the above-mentioned compounds. Further, the present invention relates to an agent for external application onto the skin, oral cavity compositions, bath additives, etc.
2. Prior Art
Compounds with a wide variety of biological activities have been developed heretofore. In particular there are a large number of reports on compounds derived from natural materials especially from the safety point of view.
As typical compounds having biological activity, those having an inhibitory effect on production of melanin are described hereinafter.
As age advances, stains, freckles or deposition of pigment after sunburn tends to be formed, increased or settled into the skin. This is problematic particularly for the middle-aged and the elderly.
Although there are still unrevealed aspects of the mechanism of generation of such acquired pigment (melanin) deposition, it is believed that melanin pigment formation is caused by hormone abnormality and external stimuli such as ultra violet rays from sunlight, oxygen and chemical substances etc., and abnormally deposited in the skin. The development of compounds preventing the formation and deposition of this melanin is highly desired and many compounds have been developed therefor. These compounds include ascorbic acid and derivatives thereof, a placenta extract, hydroquinone, kojic acid, arbutin and ellagic acid, and further there are a large number of reports on melanin production-inhibiting components extracted from plants, and these include a chamomile extract (Matricaria chamomilla L. (Composite)) disclosed in Japanese Patent Application Laid-Open No. 8-92056, a golden flower root extract (Scutellaria baicalensis G. (Labiatae)) disclosed in Japanese Patent Application Laid-Open No. 8-104616, a cumin seed (Cuminum cyminum L. (Umbelliferae)) disclosed in Japanese Patent Application Laid-Open NO. 8-119848 and a wolo extract (Borassus flabellifera (Palmac)) disclosed in Japanese Patent Application Laid-Open No. 10-29928.
Further, the present inventors also found that a fraction obtained by purifying solvent extracts from various plants by silica gel chromatography strongly inhibits the production of melanin in B16 melanoma cells, and filed for a patent (Japanese Patent Application No. 9-254025, Aug. 15, 1997). As a substance having a labdan structure, manool, an extract of Dacrydium biforme is reported to have an inhibitory effect on production of melanin (Japanese Patent Application Laid-Open No. 6-72855). Further the inhibitory effect of derivatives thereof on melanin production is also reported (Japanese Patent Application Laid-Open Nos. 7-25754, 7-69858, 7-206625 etc.).
However, the majority of these conventional melanin production inhibitors are inadequate with respect to stability, effects, adverse side effects, etc., so a new melanin inhibitor has been desired.
Cell growth activators are now described hereinafter. In aged skin, the activity of skin cells is weakened so that wrinkles and flabby skin are formed. Recently, there are many studies in which skin cells themselves are activated and the function of the skin itself in thus activated to improve skin conditions, and attention has been paid to the development of cell growth activators for activating weakened cells as well as to the incorporation of such cell activators into an agent for external application onto the skin. Conventional materials used for imparting cell-activating activity include alpha-hydroxy acids such as glycolic acids, single-component materials such as hormones, vitamins, photosensitive elements, allantoin, etc., and extracted components including animal and plant extracts such as placenta extract, lactobacillus extract, shikon extracts, aloe extract, carrot extract, etc. Further, the present inventors also found that there is strong cell-activating activity in distillated residues of solvent extracts, etc. from various plants, and filed for a patent (Japanese Patent Application Laid-Open No. 8-284572, Oct. 8, 1996). Further, labdanum furanoid diterpenoids (WO 97/45099) are reported as cell differentiation-inducing materials having a labdan structure. However, the majority conventional materials and extracts having cell-activating activity are unsatisfactory with respect to their effects, so that they have to be applied in a large amount. Also their stability in stage is not satisfactory. Moreover, they may create safety problems because of their stimulating properties or similar nature.
Anti-bacterial agents are now described hereinafter. A large number of microorganisms are present on the skin and many of them are not problematic to a healthy skin, but under bad skin conditions or bad general conditions, these microorganisms invade hair follicles, sweat glands and damaged sites to act as causative agents for infections.
In addition, there are some microorganisms which cause body odors or dandruff or oxidize secreted lipids to exert adverse effects an causative factors for acne. To kill such microorganisms, many compounds have been used, but many of them are chemically synthesized products, so there has been a demand for highly safe anti-bacterial agents derived from natural sources.
The anti-bacterial activity of Cistus absolute as one of the extracts from Cistus ladaniferus L., Cistus creticus L., Cistus monoperiensis L., Cistus salvifolius, etc. has already been reported (Nippon Keshohin Gijyutusha Kaishi, 27, 227 (1993)), but its active ingredient is not referred to therein.